This resubmitted application addresses the weaknesses identified in its initial review. Prepared in response to PAS-09-001, Drug Abuse Epidemiology and Services Research in Cooperation with the Clinical and Translational Science Awards Consortium (R01), the application lays plans to develop, test, and disseminate an interactive program to delay the onset of drug use and to prevent harmful use and abuse among Hispanic youths. Study participants will come from Northern Manhattan, home to a large population of Hispanic families from Dominican, Puerto Rican, and other backgrounds. Grounded in bicultural competence and social learning theories, the prevention program will equip youths with cognitive and behavioral skills to address ethnic-specific and pan-ethnic risk and protective factors associated with drug use among Hispanic adolescents. Youths will access the program's 10 initial sessions and annual booster sessions via personal computer. Through a human simulation interaction platform, the program will employ artificial intelligence, graphic portrayals of emotional states, and a branched learning environment in which youths can acquire, try out, receive feedback on, and master new interpersonal skills. Cultural content woven into every programmatic session, together with sessions expressly dedicated to issues of acculturation, Hispanic traditions, and bicultural stress will give the program thematic coherence and enhance its attraction and value. The study design is a randomized clinical trial. Enrolled 11-, 12-, and 13-year-old youths will complete baseline measures, intervention-arm youths will receive the initial prevention program, and all youths will complete post-intervention and 12-, 24-, and 36-month follow-up measures. Intervention-arm youths will additionally receive pairs of booster sessions after they complete 12- and 24-month follow-up measurements. Hypothesis testing analyses will examine 30-day drug use rates between arms and across follow-up measurement occasions. In addition, we will analyze intervention effects on mediator variables associated with drug use risk and protective factors. We also will assess the extent to which changes on mediator variables explain drug use differences. And, we will examine gender differences, and, to the extent possible, immigration status and ethnic background differences in study outcomes. At the conclusion of the trial, and assuming that longitudinal findings support the tested prevention approach, we will revise the program to increase its appeal for Hispanic youth across America, and we will disseminate the revised program through a variety of online resources. Throughout, we will monitor program dissemination.